CAMBRIDGE, Mass.—With a goal of accelerating the
development
of research methods and discoveries in mammalian single-cell genomics, the
Broad Institute and South San Francisco-based Fluidigm Corp. announced May 21
the launch of a new research center.

The Single-Cell Genomics Center (SCGC) will be housed at the
Broad Institute's campus in Massachusetts and will feature a complete suite of
Fluidigm single-cell tools, protocols and technologies, most notably
the
BioMark HD System. The center is also expected to act as a hub for
collaboration among single-cell genomics researchers in such areas as stem
cells and cancer biology.

The idea for the center grew out of ongoing collaborations
between
the Broad Institute and Fluidigm that involve multiple genomic
platforms. More than that, though, "the creation of the SCGC at the Broad
Institute is
one of the latest announcements regarding Fluidigm and single-cell
research, but is part of a progression of activities in this area that have
contributed to the rapid growth of single-cell research over the past few
years," Howard High, director of corporate communications at Fluidigm, tells
ddn. "Among those steps was the adoption of Fluidigm
technology by thought leaders in single-cell research and their ability to
publish
numerous provocative, single-cell, peer-reviewed papers; then the
acceptance of Fluidigm technology to conduct single-cell research by a broader
researchers; and then late last year NIH and other funding bodies allocating
funds specially targeted for single-cell research."

The idea of heterogeneity among cells in tissue samples and
other populations in not a new revelation for
researchers, but this cellular
variability is masked by averaging data across pooled cell samples, the Broad
and Fluidigm note. They explain that the
ability to tease out single-cell
genomic data has historically been limited by a lack of standardized, user-friendly
methods that would allow the
broader biological and clinical communities to
study individual cellular variability at high definition, high throughput and
low cost.

Advances in technology such as Fluidigm's microfluidic chips
and high-throughput instruments have made single-cell studies feasible by
converting
cellular heterogeneity from a source of background noise to "a
source of information enabling cutting-edge discoveries."

"With the Single-Cell Genomics Center, we will enable
researchers to access the exciting new world of single-cell
genomics, catalyze
discoveries and advance our understanding of this important area of biology,"
said Dr. Wendy Winckler, director of the Genetic
Analysis Platform at the Broad
Institute, in the news release about the collaboration.

Fluidigm
's technology reportedly provides the capabilities
required to analyze single cells—such as microfluidics and sensitivity at the
nanoscale level—as
well as parallel processing of a large number of cells and
interrogation of a large number of gene targets.

"The cell is the fundamental unit of life, and through
greater understanding of it, researchers can make breakthroughs in
large and
important fields, such as cancer diagnosis and therapy, stem cell biology,
vaccine development and even the mounting battle against drug-
resistant
bacteria. We expect this center to inspire, enable and accelerate efforts in
the emerging field of single-cell research," said Gajus
Worthington, president
and CEO of Fluidigm, in an official statement.

Taking a single-cell
genomics route can quickly lead to the
need to run tens of thousands of samples, and Fluidigm's chips can run
approximately 10,000 experiments in
parallel at a time, High points out.

"Especially for single-cell research, Fluidigm technology is
the
only one available today that can deliver the sensitivity you need at the
single-cell level, with the high throughput that allows you to process huge
numbers of cells, and run many complex tests that allow you to study many
genes," High maintains. "So we had the right technology, and as for pairing
with the Broad—well, it's the Broad, which is one of the premier biological
research organizations in the world. For Fluidigm, it was a great
opportunity
to work with a great organization."

High notes that the Broad is dedicating
scientists,
equipment and facilities to the SCGC, but Fluidigm has also placed one of its
senior scientists, Dr. Ken Livak, at the institute to oversee
the SCGC.

Through this collaborative effort, the researchers at the
SCGC intend to develop novel
single-cell, microfluidic approaches for gene
expression profiling, RNA/DNA sequencing and epigenetic analysis. The goal of
these efforts is to make
single-cell research accessible to the greater
scientific community by developing and disseminating new workflows, reagents,
bioinformatics tools and
data sets.

In the end, the Broad and Fluidigm expect that these
advances will allow deeper
exploration of the underlying causes of many
diseases, including the progression of individual cancers, differential immune
responses and the
maturation of stem cells.

"Our intent is to establish the center as a focal point to
enhance
collaboration and accelerate the science, applications, methods and
discoveries in single-cell genomics research," said Livak, Fluidigm's senior
scientific fellow, who will act as the alliance manager at the Broad Institute,
overseeing research projects amongst the center and project partners.
"Our
efforts with the Broad Institute in forming a center that specifically focuses
on single-cell research represent a big step forward for this
emerging area of
biological research."

Broad Institute study provides new clues about cancer
cell
metabolism

CAMBRIDGE, Mass.—In a study recently published in the
journal Science, researchers from the
Broad Institute and Massachusetts General Hospital (MGH) looked across 60
well-studied
cancer cell lines, analyzing which of more than 200 metabolites
were consumed or released by the fastest-dividing cells, yielding the first
large-scale
atlas of cancer metabolism. According to the researchers, their
work also points to a key role for the smallest amino acid, glycine, in cancer
cell
proliferation.

Senior author Vamsi Mootha, co-director of the Broad
Institute's Metabolism Program and
a professor at Harvard Medical School and
MGH, and his colleagues developed a technique known as CORE (COnsumption and
RElease) profiling, which
allowed them to measure the flux of metabolites—the
precursors and products of chemical reactions taking place in the body. The
team applied CORE
profiling to the NCI-60, a collection of 60 cancer cell lines
that have been studied by the scientific community for many decades. Data about
drug
sensitivity, the activity of genes and proteins, rates of cell division
and much more are publicly available for these cell lines, which represent nine
tumor types. The team's compendium of information about metabolites has also
been made publicly available.

"Using CORE, we can quantitatively determine exactly how
much of every metabolite is being consumed or released on a per-
cell, per-hour
basis," says co-first author Mohit Jain, a postdoctoral fellow in the Mootha
laboratory. "We can now start to derive flux or transport
of nutrients into or
out of the cell."

One of the most striking results of the new data is how
the
pattern of glycine consumption relates to the speed of cancer-cell division. In
the slowest-dividing cells, small amounts of glycine are released
into the
culture media. But in cancer cells that are rapidly dividing, glycine is
rapaciously consumed. The researchers note that very few metabolites
have this
unusual pattern of "crossing the zero line," meaning that rapidly dividing
cancer cells consume the metabolite while slowly dividing cells
actually
release it.

In addition to looking for metabolites that correlated with
rates of cell
division, the team also looked at the expression of almost 1,500
metabolic enzymes. Enzymes required for biosynthesis of glycine within the
mitochondria were among the most highly correlated.

"We have two independent methods—metabolite profiling as
well as gene expression
profiling—both of which point to glycine metabolism as
being important for rate of proliferation," says Mootha.

"This method offers a way of getting a quick overview of a
particular cell type or tissue, allowing you to see what a cell requires to
survive or grow," says Nilsson. "We're interested in applying this in other
settings, to liver cells and muscle tissue and to study conditions such
as
diabetes. There are lots of potential applications."